Serum IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha in schizophrenic patients, relation with symptomatology and responsiveness to risperidone treatment.

Activation of the inflammatory response system and varied levels of cytokines in acute schizophrenia have been suggested by recent studies. Psychopharmacologic agents can differentially effect cytokine production, which suggests that therapeutic function of neuroleptics may involve immunomodulation. The present study was carried out to examine: (i) serum concentrations of interleukin (IL)-1beta, soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8 and tumour necrosis factor (TNF)-alpha in schizophrenic patients; (ii) their relation with psychopathological assessment; and (iii) the relation of the initial cytokine levels with responsiveness to risperidone therapy. Thirty-four drug-free schizophrenic patients with acute exacerbation and 23 age- and gender-matched healthy controls were recruited for this study. Psychopathological assessments at admission and throughout risperidone treatment for 60 days were recorded. Serum cytokine concentrations were determined with chemilumunescence assays. According to our results, serum IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha concentrations adjusted for age, gender, body mass index and smoking were no different in patients with schizophrenia and controls and among subtypes of schizophrenia. However, the initial TNF-alpha concentrations had a significant effect on Brief Psychiatric Rating Scale and Scale Assessment of Positive Symptoms scores. The initial cytokine concentrations of the patients responsive to risperidone were not significantly different from those of non-responsive patients. The present study demonstrates that plasma levels of IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha adjusted for confounding factors are not altered in drug-free schizophrenic patients at acute exacerbation. We suggest that, if cytokine production is altered in schizophrenia, these alterations may not be detectable in systemic circulation. According to our results, the therapeutic effect of risperidone is not related to basal levels of the aforementioned cytokines. However, serum TNF-alpha may contribute to symptomatology in schizophrenia

Cytochrome P4502C9 genotype in Southeast Anatolia and possible relation with some serum tumour markers and cytokines.

Substrates for CYP2C9 include fluoxetine, phenytoin, warfarin, losartam and numerous nonsteroidal anti-inflammatory drugs. Polymorphisms in the coding region of the CYP2C9 gene produce variants at amino-acid residues 144 Arg/Cys and 359 Ile/Leu of the CYP2C9 protein. Individuals homozygous for Leu359 have markedly diminished metabolic capacities for most CYP2C9 substrates, the frequency of this allele is, however, rather low. Consistently with the modulation of enzyme activity by genetic and other factors, wide interindividual variability occurs in the elimination and/or dosage requirements of prototypic CYP2C9 substrates. The polymorphic enzyme CYP2C9 takes part in the metabolism of alkylating agents and polycyclic aromatic hydrocarbons like benzo(a)pyrene, a carcinogen present in tobacco smoke. Although the impact of impaired enzyme activity in metabolism of carcinogens and procarcinogens has not been fully defined, an association of CYP2C9 variant alleles to DNA adduct levels in lung tissues as well as to lung cancer risk have been reported. In this study 64 healthy subjects (44M/22F) were analysed for CYP2C9 genotype with PCR-RFLP and for serum carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), CA 19-9, CA 15-3, ferritin, IL-6, IL-8 concentrations by chemiluminescence or electrochemiluminescence methods. CYP2C9*1 was found to be the most prevalent allele and CYP2C9*1/CYP2C9*1 was the most frequent genotype represented in 64% of the population in southeastern Anatolia (Gaziantep). Although slight differences in serum tumour marker and cytokine concentrations were observed for CYP2C9 genotypes the differences were statistically insignificant (P > 0.05). This could be due to the complexity of the role of CYP2C9 in benzo(a)pyrene metabolism as well as from other contributing factors like interindividual variability of diverse enzymes participating in the same metabolic pathway, unequal expression of the variant alleles and differences in exposure to carcinogens. However, determination of CYP2C9 phenotypes in a larger group of subjects might clarify these slight differences.

Mediators of inflammation in children with type I diabetes mellitus: cytokines in type I diabetic children.

OBJECTIVES: Recent evidence favors primary role of cellular autoimmunity and its humoral mediators in pathogenesis and following Type I diabetes mellitus (DM). The present study was carried out to investigate serum concentrations of C-reactive protein (CRP), interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-alpha in children with type I DM. Potential role of lipid metabolism, glycemic control, body mass index (BMI) and disease duration were evaluated. DESIGN AND METHODS: Thirty-five children with type I DM and 30 age and gender matched nondiabetic controls were recruited for this study. RESULTS: Circulating IL-8 levels were elevated in children with type I DM (12.7 +/- 1.7 pg/mL) compared with nondiabetic controls (5.5 +/- 0.3 pg/mL) and the difference remained significant after adjustment for cofactors and covariates (p: 0.033). Although statistically insignificant serum CRP concentrations were slightly higher in diabetic children (p: 0.075). Serum TNF-alpha and IL-6 levels were comparable in diabetic and nondiabetic groups. However newly diagnosed (<1 yr) cases had higher TNF-alpha and IL-6 levels compared to cases with longer standing DM. In diabetic children BMI was independently associated with an increase in serum IL-8 levels. Serum CRP, lipids, apolipoproteins and glycemic control were not significant predictors of cytokine concentrations in children with type I DM. CONCLUSION: Circulating levels of IL-8 were elevated and were correlated with BMI in children with type I DM, hinting perhaps at adipose tissue as a site of production. Elevated systemic IL-6 and TNF-alpha were limited to newly diagnosed cases suggesting activation of the inflammatory immune response system at early stages of the disease.

Diagnostic value of biochemical markers of bone turnover and postmenopausal osteoporosis.

We studied 77 women divided into postmenopausal osteoporotic and premenopausal and postmenopausal non-osteoporotic groups in order to evaluate bone metabolism and diagnostic value of biochemical markers of bone turnover in postmenopausal osteoporosis. Postmenopausal osteoporotic (n: 40), postmenopausal non-osteoporotic (n: 24) and premenopausal non-osteoporotic (n: 13) groups were defined according to bone mineral density (BMD) scores obtained with dual energy X-ray absorptiometry (DEXA). Urinary deoxy-pyridinoline (Dpd), pyridinoline (Pyd), serum total alkaline phosphatase (ALP), bone specific alkaline phosphatase (BALP), osteocalcin (BGP), total calcium, phosphorus, and creatinine levels were determined. Urinary Dpd and Pyd levels of postmenopausal osteoporotic group (8.7 and 18.7 mumol/mg creatinine) were significantly higher than postmenopausal control (5.1 and 11.7 mumol/mg creatinine, p < 0.0001) and premenopausal control (6.0 and 13.0 mumol/mg creatinine, p < 0.0005 and p < 0.001) groups. Bone formation markers were not significantly different between groups, although BGP correlated with Dpd and Pyd (r: 0.26 and r: 0.31, p < 0.05) in osteoporotic subjects. From receiver operating curve (ROC) analysis Dpd had the best diagnostic value (0.846), followed by Pyd (0.802) in evaluation of osteoporosis, whereas BALP (0.570) and BGP (0.528) were relatively inefficient in the discrimination of postmenopausal osteoporosis. This study suggests that bone resorption markers are more efficient than bone formation markers in the diagnosis of postmenopausal osteoporosis. Urinary Dpd/creatinine ratio has the highest diagnostic value.

Menstrual cycle dependent variability for serum tumor markers CEA, AFP, CA 19-9, CA 125 and CA 15-3 in healthy women.

Information on menstrual cycle dependent variation of tumor markers in healthy women is a subject of diagnostic efficiency and has an impact in elucidating the normal function of these markers. In this study midfollicular and midluteal concentrations of serum CEA, AFP, CA 19-9, CA 125, CA 15-3 and their relations with LH, FSH, prolactin, estradiol and progesterone were evaluated during ovulatory cycles in a group of 23 healthy female individuals. Samples were collected on the 7th and 21st day of the same menstrual cycle. Tumor marker and hormone concentrations were determined with chemiluminescence or electrochemiluminescence EIA methods. A significant phase-dependent difference was observed for CA 15-3, midluteal concentrations (mean +/- SEM; 26.33 +/- 1.56 U/ml) higher than the midfollicular (mean +/- SEM; 19.27 +/- 1.49 U/ml) concentrations (p < 0.001). But an obvious difference for other tumor markers investigated did not exist. Significant correlations of follicular and luteal CA 125 levels with body mass index of the subjects were observed (r:0.52, p < 0.05 and r:0.57, p < 0.005, respectively). CA 15-3 antigen is a product of the MUC-1 gene which is expressed in abundance by endometrial epithelial cells in the secretory phase of the menstrual cycle which may be the potential source of variability. The association of CA 125 levels with obesity suggests a possible role of adipose tissue in CA 125 metabolism. In conclusion our data suggest that in healthy women serum CA 15-3 levels are significantly elevated in the midluteal phase of the menstrual cycle compared to midfollicular phase. Therefore, consideration of menstrual cycle dependent variability for CA 15-3 appears indicated in interpretation of individual results.